PROJECT SUMMARY/ABSTRACT?Developmental Funds During the current reporting period (2013 - 2017), SJCCC awarded $4,060,094 in Developmental Funds to meet two Specific Aims: to support pilot projects for new and established SJCCC investigators, and to support developing Shared Resources. In the pilot project category, $3,834,745 was awarded to 33 pilot projects, representing a 62% increase over the previous funding period. In the developing Shared Resource category, $225,349 was awarded to one developing Shared Resource: Radiation Dosimetry Core. Of the $4,060,094 total distributed to pilot projects and the developing Shared Resource, $2,101,243 (52%) came from CCSG funds and $1,958,851 (48%) was provided by the institution. These 33 pilot projects have had a significant impact in the Center by establishing the laboratory and research programs of new members including Moldoveanu (CBP) and Zhu (DBSTP); promoting interprogrammatic collaborations such as work from Yang and Robinson (HMP, NBTP) and intraprogrammatic collaborations such as Gawad's work with Inaba, Pui, Mullighan, Evans and Yang (HMP); translating findings into clinical protocols such as the BMNIRN trial (NCT02392793) based on findings from Shelat (CBP); and supporting unique external collaborations such as melanoma studies from Pappo (DBSTP) and Dr. John Kirkwood of UPMC Hillman Cancer Center. External awards received by pilot project recipients during the reporting period that resulted from data generated by Developmental Funds support totals $19,913,112, a 1:5 return on investment. Advances across Programs from pilot projects include Mittag's (CBP) study on the biophysical mechanisms of Gli ubiquitination in shaping Hedgehog signaling in cancer (successful R01 application); McKinney-Freeman's (CBP) work on NFI genes in hematopoietic stem cells (successful R01 application); Moldoveanu's (CBP) identification of BCL-2 family functions (publications in Cell and Nature Cell Biology); Zuo's (NBTP) discovery regarding the otoprotective effect of amifostine against cisplatin-induced hearing loss (successful R01 application); Northcott's (NBTP) characterization of transcription factor mutations as drivers in pediatric medulloblastoma (publication in Nature and $600,000 in grant support); Klco's (HMP) identification of genomic alterations in pediatric myelodysplastic syndromes (Nature Communications); Yang and Robinson's (HMP, NBTP) interprogrammatic project on inherited genetic variations in susceptibility to platinum ototoxicity (Nature Genetics); and Federico's (DBSTP) project targeting the P13K pathway in neuroblastoma that provided the foundation for Stewart et al., Nature 2017. Future plans include a special emphasis on funding clinical and population science research through the pilot project mechanism and support of a developing Shared Resource, the Center for Advanced Genomic Editing (CAGE). This Shared Resource was established to provide expertise and infrastructure to educate, assist, expedite, and perform established and emerging genome-engineering technologies, including CRISPR/Cas9 and other nuclease platforms.